IGF2BP2 Shapes the Tumor Microenvironment by Regulating Monocyte and Macrophage Recruitment in Bladder Cancer
ABSTRACT Background Immunotherapy has shown promise for bladder cancer (BC) treatment but is effective only in a subset of patients. Understanding the tumor microenvironment (TME) and its regulators, such as the expression of N6‐methyladenosine (m6A) regulators, may improve therapeutic outcomes. Thi...
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| Format: | Article |
| Language: | English |
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Wiley
2024-12-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.70506 |
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| _version_ | 1832593687710793728 |
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| author | Jianpeng Li Yunzhong Jiang Minghai Ma Lu Wang Minxuan Jing Zezhong Yang Lizhao Wang Quanpeng Qiu Rundong Song Yuanchun Pu Yuanquan Zhang Nan Mei Mengzhao Zhang Jinhai Fan |
| author_facet | Jianpeng Li Yunzhong Jiang Minghai Ma Lu Wang Minxuan Jing Zezhong Yang Lizhao Wang Quanpeng Qiu Rundong Song Yuanchun Pu Yuanquan Zhang Nan Mei Mengzhao Zhang Jinhai Fan |
| author_sort | Jianpeng Li |
| collection | DOAJ |
| description | ABSTRACT Background Immunotherapy has shown promise for bladder cancer (BC) treatment but is effective only in a subset of patients. Understanding the tumor microenvironment (TME) and its regulators, such as the expression of N6‐methyladenosine (m6A) regulators, may improve therapeutic outcomes. This study focuses on the role of IGF2BP2, an m6A reader, in modulating the BC TME. Methods Transcriptomic and single‐cell RNA‐seq data from public databases were analyzed to identify BC subgroups and investigate IGF2BP2's role in the TME. Clustering and PCA identified key m6A regulators. NicheNet and SCENIC analyses were used to predict cell–cell interactions and transcriptional regulators, respectively. IGF2BP2's role in macrophage recruitment was validated via co‐culture experiments and RNA sequencing. Results Unsupervised clustering identified BC subgroups with distinct TME characteristics, with IGF2BP2 emerging as a key regulator associated with poor prognosis and reduced response to immunotherapy. Single‐cell analysis revealed IGF2BP2's high expression in the GE‐9 epithelial subpopulation, characterized by immune evasion features and cytokine‐mediated macrophage recruitment. NicheNet analysis showed that GE‐9 cells interact with monocyte/macrophage populations through cytokine signaling. Co‐culture experiments confirmed IGF2BP2's role in recruiting macrophages, partially mediated by CCL2. Furthermore, IGF2BP2 expression was linked to immunosuppressive M2‐like and SPP1+ macrophages, contributing to an angiogenesis‐promoting and immunosuppressive TME. Conclusion IGF2BP2 shapes the BC TME by modulating macrophage infiltration and polarization, leading to an immunosuppressive microenvironment that hinders immunotherapy. Targeting IGF2BP2 could enhance the efficacy of current therapies and improve patient outcomes. |
| format | Article |
| id | doaj-art-7b8ad691b8ad4b03916de0fafe051734 |
| institution | Kabale University |
| issn | 2045-7634 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-7b8ad691b8ad4b03916de0fafe0517342025-01-20T10:51:32ZengWileyCancer Medicine2045-76342024-12-011324n/an/a10.1002/cam4.70506IGF2BP2 Shapes the Tumor Microenvironment by Regulating Monocyte and Macrophage Recruitment in Bladder CancerJianpeng Li0Yunzhong Jiang1Minghai Ma2Lu Wang3Minxuan Jing4Zezhong Yang5Lizhao Wang6Quanpeng Qiu7Rundong Song8Yuanchun Pu9Yuanquan Zhang10Nan Mei11Mengzhao Zhang12Jinhai Fan13Department of Urology First Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi ChinaDepartment of Urology First Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi ChinaDepartment of Urology First Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi ChinaDepartment of Urology First Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi ChinaDepartment of Urology First Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi ChinaDepartment of Urology First Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi ChinaDepartment of Breast Surgery First Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi ChinaDepartment of General Surgery First Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi ChinaDepartment of Urology First Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi ChinaDepartment of Urology First Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi ChinaDepartment of Urology First Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi ChinaDepartment of Hematology First Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi ChinaDepartment of Vascular Surgery First Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi ChinaDepartment of Urology First Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi ChinaABSTRACT Background Immunotherapy has shown promise for bladder cancer (BC) treatment but is effective only in a subset of patients. Understanding the tumor microenvironment (TME) and its regulators, such as the expression of N6‐methyladenosine (m6A) regulators, may improve therapeutic outcomes. This study focuses on the role of IGF2BP2, an m6A reader, in modulating the BC TME. Methods Transcriptomic and single‐cell RNA‐seq data from public databases were analyzed to identify BC subgroups and investigate IGF2BP2's role in the TME. Clustering and PCA identified key m6A regulators. NicheNet and SCENIC analyses were used to predict cell–cell interactions and transcriptional regulators, respectively. IGF2BP2's role in macrophage recruitment was validated via co‐culture experiments and RNA sequencing. Results Unsupervised clustering identified BC subgroups with distinct TME characteristics, with IGF2BP2 emerging as a key regulator associated with poor prognosis and reduced response to immunotherapy. Single‐cell analysis revealed IGF2BP2's high expression in the GE‐9 epithelial subpopulation, characterized by immune evasion features and cytokine‐mediated macrophage recruitment. NicheNet analysis showed that GE‐9 cells interact with monocyte/macrophage populations through cytokine signaling. Co‐culture experiments confirmed IGF2BP2's role in recruiting macrophages, partially mediated by CCL2. Furthermore, IGF2BP2 expression was linked to immunosuppressive M2‐like and SPP1+ macrophages, contributing to an angiogenesis‐promoting and immunosuppressive TME. Conclusion IGF2BP2 shapes the BC TME by modulating macrophage infiltration and polarization, leading to an immunosuppressive microenvironment that hinders immunotherapy. Targeting IGF2BP2 could enhance the efficacy of current therapies and improve patient outcomes.https://doi.org/10.1002/cam4.70506bladder cancerepithelial cellIGF2BP2m6Amacrophagetumor infiltration immune cells |
| spellingShingle | Jianpeng Li Yunzhong Jiang Minghai Ma Lu Wang Minxuan Jing Zezhong Yang Lizhao Wang Quanpeng Qiu Rundong Song Yuanchun Pu Yuanquan Zhang Nan Mei Mengzhao Zhang Jinhai Fan IGF2BP2 Shapes the Tumor Microenvironment by Regulating Monocyte and Macrophage Recruitment in Bladder Cancer Cancer Medicine bladder cancer epithelial cell IGF2BP2 m6A macrophage tumor infiltration immune cells |
| title | IGF2BP2 Shapes the Tumor Microenvironment by Regulating Monocyte and Macrophage Recruitment in Bladder Cancer |
| title_full | IGF2BP2 Shapes the Tumor Microenvironment by Regulating Monocyte and Macrophage Recruitment in Bladder Cancer |
| title_fullStr | IGF2BP2 Shapes the Tumor Microenvironment by Regulating Monocyte and Macrophage Recruitment in Bladder Cancer |
| title_full_unstemmed | IGF2BP2 Shapes the Tumor Microenvironment by Regulating Monocyte and Macrophage Recruitment in Bladder Cancer |
| title_short | IGF2BP2 Shapes the Tumor Microenvironment by Regulating Monocyte and Macrophage Recruitment in Bladder Cancer |
| title_sort | igf2bp2 shapes the tumor microenvironment by regulating monocyte and macrophage recruitment in bladder cancer |
| topic | bladder cancer epithelial cell IGF2BP2 m6A macrophage tumor infiltration immune cells |
| url | https://doi.org/10.1002/cam4.70506 |
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